The introduction of radiotherapy has represented a considerable step forward in the treatment of intraocular tumors, substituting the radical operation of the eye enucleation. Preservative radiotherapy treatments indeed allow preserving the integrity of the eye and maintaining its residual visual capacity, without compromising the survival of the patient and without the onset of secondary metastasis.
Proton therapy is considered the treatment of choice for ocular tumors due to the extreme spatial selectivity and to the advantageous modes for supplying the treatment. Proton beams indeed allow obtaining a spatial distribution of the radiation dose highly in accordance with the volume to be treated, which in the case of ocular pathologies can have very reduced size, even equal to a few millimeters. In addition, ocular tumors are often localized in the rear pole of the eye, near very sensitive structures such as the optical disc and the fovea; due to the high dose gradients, proton therapy treatments allow completely saving as much as possible the critical ocular structures, thereby maintaining the patient's visual capacities intact.
In addition to proton therapy, one of the most widespread radiotherapy techniques for the treatment of ocular tumors is stereotactic photon radiotherapy. Stereotactic radiotherapy employs multiple, focused high-energy photon beams with high geometric precision on the tumor region to be treated. Such technique allows obtaining very high dose gradients, thus limiting the irradiation of the surrounding healthy tissues.
The therapeutic effectiveness and quality of such treatments are closely related to the accuracy of the localization of the ocular lesion and to the compensation of the eye movements, which a patient may make even involuntarily during administration of radiation.
Clearly, it is critical to evaluate with high precision, during the planning step of a treatment, the distribution in the eye of the ocular tissues to the treated, and during the treatment, i.e. during the administration of a radiation dose, the position of the patient's eye with respect to the incident radiation beam. Such evaluation is important for allowing the irradiation of only the tissues to be treated, and therefore avoiding the irradiation of healthy eye tissues, so as to maintain as much as possible the visual capacity of the patient subjected to treatment.
For this purpose, over the years various control systems have been proposed, both of invasive and non-invasive type, aimed to detect the ocular position and the ocular movements during a treatment session. For example, systems have been proposed that provide for the invasive application of radiopaque clips to the margins of the treatment zone (e.g. tumor zone) for the indirect localization of the lesion by means of multiple radiographs of the eye.
Alternatively, systems for automatically controlling ocular movements have been proposed, which are based on monitoring the eye position starting from two-dimensional images acquired by a telecamera; such images contain specific ocular reflections obtained with the use of infrared sources directed towards the eye under examination.
Some of the conventional equipment provide that the administration of the radiation dose is manually interrupted if there are ocular movements by the patient under treatment, even involuntary ones. Such movements are evaluated in a qualitative manner by the doctor, typically by observing on a monitor the deviations of the eye with respect to pre-established reference borders; or they can be automatically evaluated, e.g. by estimating the eye rotation degree, starting from the pupil borders identified on the ocular images acquired by a control system as mentioned above.
In patent application US-2010/0254513, for example, a device is taught that allows bringing a reference axis (typically the optical axis) of the patient's eye into alignment with the treatment system, also by means of the use of invasive means.
In patent application US-2009/0163898, on the other hand, a telecamera and a light source are used, focused on the eye to be treated in order to identify a reference ocular axis. In particular, the reference ocular axis is that at which the center of the limbus identified on the images acquired with the telecamera coincides with a corneal reflection generated by the light source.
Patent application US-2009/0182311 teaches an equipment and a method of obtaining the alignment and stabilization of the ocular position by means of a contact lens applied to the ocular surface. The lens is connected to an articulated arm which allows positioning and aligning the eye with respect to a treatment equipment. The equipment also includes a telecamera used for verifying the centering of the contact lens with the center of the limbus and for monitoring possible movements of the eye with respect to the lens. Localizing the contact lens by means of specific sensors (radio transmitters or laser pointers), allows to find the 3D position and the orientation of the eye in a reference system outside the eye itself.
In patent application US-2009/0161826 the use of a standardized model of the human eye is described, which model is adapted to the specific patient based on the biometric parameters obtained by specific imaging techniques (funduscopy, optical tomography, MRI, etc.). The ocular model thus obtained is processed and (as the position is known of the contact lens applied on the eye to be treated) it allows determining the three-dimensional position of the ocular structures of interest (macula, optical disc, etc.) in an external reference coordinate system. This solution also allows establishing, before treatment, the amplitude and duration of the ocular movements allowed to the patient, in order to maintain the radiation dose at the critical optical structures below a certain level.
There are numerous drawbacks of such conventional systems. Some systems, as mentioned above, are invasive systems and provide for the use of auxiliary means such as contact lenses or radiopaque clips, whose application certainly causes discomfort in patients. Other systems, even if they are non-invasive, do not supply any information on the position, in a three-dimensional reference system, of the ocular lesion and the ocular structures at risk and provide for the manual interruption of the treatment based on a qualitative estimation of the ocular movements. Moreover, the treatment systems based on proton therapy, before starting the treatment procedure, require long and laborious invasive procedures for positioning the patient in order to determine the ocular region to be treated and to arrange such a region in the field of action of the radiant beam (treatment isocenter), so as to only hit the damaged zone and not the surrounding healthy tissues of the eye to be treated.
Not least, several of the abovementioned systems are standardized, in the sense that they do not provide for the personalization of the treatment system on the single patient; they require the use of fixed and isotropic thresholds on the ocular movements and the use of standardized models of the ocular structure, which thresholds and models are not “adaptable” or are adaptable to a very limited extent, often inadequate for the specific ocular morphology of the patient to be subjected to the treatment.